Disintegration of amyloid fibrils of α-synuclein by dequalinium

Jae Woo Park, In Hwan Lee, Ji Sook Hahn, Jongsun Kim, Kwang Chul Chung, Seung R. Paik

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

α-Synuclein is the major amyloidogenic component observed in the Lewy bodies of Parkinson's disease. Amyloid fibrils of α-synuclein prepared in vitro were instantaneously disintegrated by dequalinium (DQ). Double-headed cationic amphipathic structure of DQ with two aminoquinaldinium rings at both ends turned out to be crucial to exert the disintegration activity. The defibrillation activity was shown to be selective toward the fibrils of α-synuclein and Aβ40 while the other β2-microglobulin amyloid fibrils were not susceptible so much. Besides the common cross β-sheet conformation of amyloid fibrils, therefore, additional specific molecular interactions with the target amyloidogenic proteins have been expected to be involved for DQ to exhibit its defibrillation activity. The disintegrating activity of DQ was also evaluated in vivo with the yeast system overexpressing α-synuclein-GFP. With the DQ treatment, the intracellular green inclusions turned into green smears, which resulted in the enhanced cell death. Based on the data, the previous observation that DQ led to the predominant protofibril formation of α-synuclein could be explained by the dual function of DQ showing both the facilitated self-oligomerization of α-synuclein and the instantaneous defibrillation of its amyloid fibrils. In addition, amyloidosis-related cytotoxicity has been demonstrated to be amplified by the fragmentation of mature amyloid fibrils by DQ.

Original languageEnglish
Pages (from-to)1156-1161
Number of pages6
JournalBiochimica et Biophysica Acta - General Subjects
Volume1780
Issue number10
DOIs
Publication statusPublished - 2008 Oct 1

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Dequalinium
Synucleins
Disintegration
Amyloid
Amyloidogenic Proteins
Oligomerization
Molecular interactions
Amyloidosis
Cell death
Cytotoxicity
Yeast
Parkinson Disease
Conformations
Cell Death
Yeasts

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Park, Jae Woo ; Lee, In Hwan ; Hahn, Ji Sook ; Kim, Jongsun ; Chung, Kwang Chul ; Paik, Seung R. / Disintegration of amyloid fibrils of α-synuclein by dequalinium. In: Biochimica et Biophysica Acta - General Subjects. 2008 ; Vol. 1780, No. 10. pp. 1156-1161.
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Disintegration of amyloid fibrils of α-synuclein by dequalinium. / Park, Jae Woo; Lee, In Hwan; Hahn, Ji Sook; Kim, Jongsun; Chung, Kwang Chul; Paik, Seung R.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1780, No. 10, 01.10.2008, p. 1156-1161.

Research output: Contribution to journalArticle

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